{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T13:18:07Z","timestamp":1790428687294,"version":"4.1.0"},"reference-count":74,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T00:00:00Z","timestamp":1644537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003323","name":"Agence Nationale de Recherches sur le Sida et les H\u00e9patites Virales","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003323","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006103","name":"Domaine d\u2019Int\u00e9r\u00eat Majeur Logiciels et Syst\u00e8mes Complexes","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006103","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Immunological non-responders (InRs) are HIV-infected individuals in whom the administration of combination antiretroviral therapy (cART), although successful in suppressing viral replication, cannot properly reconstitute patient circulating CD4<jats:sup>+<\/jats:sup> T-cell number to immunocompetent levels. The causes for this immunological failure remain elusive, and no therapeutic strategy is available to restore a proper CD4<jats:sup>+<\/jats:sup> T-cell immune response in these individuals. We have recently demonstrated that platelets harboring infectious HIV are a hallmark of InR, and we now report on a causal connection between HIV-containing platelets and T-cell dysfunctions. We show here that <jats:italic>in vivo<\/jats:italic>, platelet\u2013T-cell conjugates are more frequent among CD4<jats:sup>+<\/jats:sup> T cells in InRs displaying HIV-containing platelets (&amp;lt;350 CD4<jats:sup>+<\/jats:sup> T cells\/\u03bcl blood for &amp;gt;1 year) as compared with healthy donors or immunological responders (IRs; &amp;gt;350 CD4<jats:sup>+<\/jats:sup> T cells\/\u03bcl). This contact between platelet containing HIV and T cell in the conjugates is not infectious for CD4<jats:sup>+<\/jats:sup> T cells, as coculture of platelets from InRs containing HIV with healthy donor CD4<jats:sup>+<\/jats:sup> T cells fails to propagate infection to CD4<jats:sup>+<\/jats:sup> T cells. In contrast, when macrophages are the target of platelets containing HIV from InRs, macrophages become infected. Differential transcriptomic analyses comparing InR and IR CD4<jats:sup>+<\/jats:sup> T cells reveal an upregulation of genes involved in both aerobic and anaerobic glycolysis in CD4<jats:sup>+<\/jats:sup> T cells from InR vs. IR individuals. Accordingly, InR platelets containing HIV induce a dysfunctional increase in glycolysis-mediated energy production in CD4<jats:sup>+<\/jats:sup> T cells as compared with T cells cocultured with IR platelets devoid of virus. In contrast, macrophage metabolism is not affected by platelet contact. Altogether, this brief report demonstrates a direct causal link between presence of HIV in platelets and T-cell dysfunctions typical of InR, contributing to devise a platelet-targeted therapy for improving immune reconstitution in these individuals.<\/jats:p>","DOI":"10.3389\/fimmu.2021.781923","type":"journal-article","created":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T07:00:31Z","timestamp":1644562831000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["HIV-Sheltering Platelets From Immunological Non-Responders Induce a Dysfunctional Glycolytic CD4+ T-Cell 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